{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:58:43Z","timestamp":1780880323090,"version":"3.54.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":53,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-48074-5","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T08:05:32Z","timestamp":1776326732000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combination of a pesco vegetarian diet with non-steroidal anti-inflammatory drugs reduces colorectal cancer risk and modulates gut microbiota in PIRC rats"],"prefix":"10.1038","volume":"16","author":[{"given":"Sofia","family":"Chioccioli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niccol\u00f2","family":"Meriggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela Mejia","family":"Monroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Renzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Cerasuolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Caderni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"De Filippo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"48074_CR1","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/s41575-019-0189-8","volume":"16","author":"N Keum","year":"2019","unstructured":"Keum, N. & Giovannucci, E. Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies. Nat. Rev. Gastroenterol. Hepatol. 16, 713\u2013732 (2019).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"48074_CR2","doi-asserted-by":"publisher","first-page":"640","DOI":"10.3390\/cancers14030640","volume":"14","author":"S Caini","year":"2022","unstructured":"Caini, S. et al. Fish consumption and colorectal cancer risk: Meta-analysis of prospective epidemiological studies and review of evidence from animal studies. Cancers 14, 640 (2022).","journal-title":"Cancers"},{"key":"48074_CR3","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1186\/s40168-024-01900-2","volume":"12","author":"C De Filippo","year":"2024","unstructured":"De Filippo, C. et al. Gut microbiota drives colon cancer risk associated with diet: A comparative analysis of meat-based and pesco-vegetarian diets. Microbiome 12, 180 (2024).","journal-title":"Microbiome"},{"key":"48074_CR4","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/S0140-6736(10)61543-7","volume":"376","author":"PM Rothwell","year":"2010","unstructured":"Rothwell, P. M. et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet 376, 1741\u20131750 (2010).","journal-title":"Lancet"},{"key":"48074_CR5","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/nrgastro.2016.56","volume":"13","author":"L Ricciardiello","year":"2016","unstructured":"Ricciardiello, L., Ahnen, D. J. & Lynch, P. M. Chemoprevention of hereditary colon cancers: Time for new strategies. Nat. Rev. Gastroenterol. Hepatol. 13, 352\u2013361 (2016).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"48074_CR6","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.3390\/ijms19082332","volume":"19","author":"A Mohammed","year":"2018","unstructured":"Mohammed, A., Yarla, N. S., Madka, V. & Rao, C. V. Clinically relevant anti-inflammatory agents for chemoprevention of colorectal cancer: New perspectives. Int. J. Mol. Sci. 19, 2332 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"48074_CR7","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1146\/annurev-med-060319-120913","volume":"72","author":"DA Drew","year":"2021","unstructured":"Drew, D. A. & Chan, A. T. Aspirin in the prevention of colorectal neoplasia. Annu. Rev. Med. 72, 415\u2013430 (2021).","journal-title":"Annu. Rev. Med."},{"key":"48074_CR8","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1158\/1940-6207.CAPR-11-0106","volume":"4","author":"J Burn","year":"2011","unstructured":"Burn, J. et al. A randomized placebo-controlled prevention trial of aspirin and\/or resistant starch in young people with familial adenomatous polyposis. Cancer Prev. Res. (Phila) 4, 655\u2013665 (2011).","journal-title":"Cancer Prev. Res. (Phila)"},{"key":"48074_CR9","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/S2468-1253(21)00018-2","volume":"6","author":"H Ishikawa","year":"2021","unstructured":"Ishikawa, H. et al. Chemoprevention with low-dose aspirin, mesalazine, or both in patients with familial adenomatous polyposis without previous colectomy (J-FAPP Study IV): A multicentre, double-blind, randomised, two-by-two factorial design trial. Lancet Gastroenterol. Hepatol. 6, 474\u2013481 (2021).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"48074_CR10","doi-asserted-by":"publisher","first-page":"znae070","DOI":"10.1093\/bjs\/znae070","volume":"11","author":"G Zaffaroni","year":"2024","unstructured":"Zaffaroni, G. et al. Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: A joint EHTG-ESCP revision. Br. J. Surg. 11, znae070 (2024).","journal-title":"Br. J. Surg."},{"key":"48074_CR11","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1056\/NEJM199305063281805","volume":"328","author":"FM Giardiello","year":"1993","unstructured":"Giardiello, F. M. et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N. Engl. J. Med. 328, 1313\u20131316 (1993).","journal-title":"N. Engl. J. Med."},{"key":"48074_CR12","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1186\/s12885-015-1627-9","volume":"15","author":"AP Femia","year":"2015","unstructured":"Femia, A. P. et al. Sulindac, 3,3\u2019-diindolylmethane and curcumin reduce carcinogenesis in the Pirc rat, an Apc-driven model of colon carcinogenesis. BMC Cancer 15, 611 (2015).","journal-title":"BMC Cancer"},{"key":"48074_CR13","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1186\/s12885-020-07311-4","volume":"20","author":"JS Davis","year":"2020","unstructured":"Davis, J. S. et al. Sulindac plus a phospholipid is effective for polyp reduction and safer than sulindac alone in a mouse model of colorectal cancer development. BMC Cancer 20, 871 (2020).","journal-title":"BMC Cancer"},{"key":"48074_CR14","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1053\/j.gastro.2020.05.004","volume":"159","author":"R Zhao","year":"2020","unstructured":"Zhao, R. et al. Aspirin reduces colorectal tumor development in mice and gut microbes reduce its bioavailability and chemopreventive effects. Gastroenterology 159, 969-983.e4 (2020).","journal-title":"Gastroenterology"},{"key":"48074_CR15","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1186\/s13063-019-3801-x","volume":"20","author":"F Sofi","year":"2019","unstructured":"Sofi, F. et al. Fecal microbiome as determinant of the effect of diet on colorectal cancer risk: Comparison of meat-based versus pesco-vegetarian diets (the MeaTIc study). Trials 20, 688 (2019).","journal-title":"Trials"},{"key":"48074_CR16","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1111\/jgh.15042","volume":"36","author":"N Abu-Ghazaleh","year":"2021","unstructured":"Abu-Ghazaleh, N., Chua, W. J. & Gopalan, V. Intestinal microbiota and its association with colon cancer and red\/processed meat consumption. J. Gastroenterol. Hepatol. 36, 75\u201388 (2021).","journal-title":"J. Gastroenterol. Hepatol."},{"key":"48074_CR17","doi-asserted-by":"publisher","first-page":"4542","DOI":"10.1158\/0008-5472.CAN-05-4428","volume":"66","author":"BS Reddy","year":"2006","unstructured":"Reddy, B. S. et al. Prevention of azoxymethane-induced colon cancer by combination of low doses of atorvastatin, aspirin, and celecoxib in F 344 rats. Cancer Res. 66, 4542\u20134546 (2006).","journal-title":"Cancer Res."},{"key":"48074_CR18","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1097\/CEJ.0b013e32834dbbfd","volume":"21","author":"P Zhou","year":"2012","unstructured":"Zhou, P., Cheng, S. W., Yang, R., Wang, B. & Liu, J. Combination chemoprevention: Future direction of colorectal cancer prevention. Eur. J. Cancer Prev. 21, 231\u2013240 (2012).","journal-title":"Eur. J. Cancer Prev."},{"key":"48074_CR19","doi-asserted-by":"publisher","first-page":"175656","DOI":"10.1016\/j.ejphar.2023.175656","volume":"946","author":"KY Liu","year":"2023","unstructured":"Liu, K. Y., Wang, Q., Nakatsu, C. H., Jones-Hall, Y. & Jiang, Q. Combining gamma-tocopherol and aspirin synergistically suppresses colitis-associated colon tumorigenesis and modulates the gut microbiota in mice, and inhibits the growth of human colon cancer cells. Eur. J. Pharmacol. 946, 175656 (2023).","journal-title":"Eur. J. Pharmacol."},{"key":"48074_CR20","doi-asserted-by":"publisher","first-page":"16514","DOI":"10.1073\/pnas.1323064111","volume":"111","author":"JM Amos-Landgraf","year":"2014","unstructured":"Amos-Landgraf, J. M. et al. Sex disparity in colonic adenomagenesis involves promotion by male hormones, not protection by female hormones. Proc. Natl. Acad. Sci. U. S. A. 111, 16514\u201316519 (2014).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"48074_CR21","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1093\/carcin\/20.5.805","volume":"20","author":"SL Williamson","year":"1999","unstructured":"Williamson, S. L. et al. Intestinal tumorigenesis in the Apc1638N mouse treated with aspirin and resistant starch for up to 5 months. Carcinogenesis 20, 805\u2013810 (1999).","journal-title":"Carcinogenesis"},{"key":"48074_CR22","first-page":"269","volume":"62","author":"CH Chiu","year":"2000","unstructured":"Chiu, C. H., McEntee, M. F. & Whelan, J. Discordant effect of aspirin and indomethacin on intestinal tumor burden in Apc(Min\/+) mice. PLEFA 62, 269\u2013275 (2000).","journal-title":"PLEFA"},{"key":"48074_CR23","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/S0039-6060(98)70124-2","volume":"124","author":"NN Mahmoud","year":"1998","unstructured":"Mahmoud, N. N. et al. Aspirin prevents tumoursin a murine model of familial adenomatous polyposis. Surgery 124, 225\u2013231 (1998).","journal-title":"Surgery"},{"key":"48074_CR24","doi-asserted-by":"publisher","first-page":"4036","DOI":"10.1073\/pnas.0611690104","volume":"104","author":"JM Amos-Landgraf","year":"2007","unstructured":"Amos-Landgraf, J. M. et al. A target-selected Apc-mutant rat kindred enhances the modeling of familial human colon cancer. Proc. Natl. Acad. Sci. U. S. A. 104, 4036\u20134041 (2007).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"48074_CR25","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","volume":"22","author":"S Reagan-Shaw","year":"2008","unstructured":"Reagan-Shaw, S., Nihal, M. & Ahmad, N. Dose translation from animal to human studies revisited. FASEB J. 22, 659\u2013661 (2008).","journal-title":"FASEB J."},{"key":"48074_CR26","doi-asserted-by":"publisher","first-page":"E488","DOI":"10.1002\/ijc.29232","volume":"136","author":"AP Femia","year":"2015","unstructured":"Femia, A. P., Luceri, C., Soares, P. V., Lodovici, M. & Caderni, G. Multiple mucin depleted foci, high proliferation and low apoptotic response in the onset of colon carcinogenesis of the PIRC rat, mutated in Apc. Int. J. Cancer 136, E488\u2013E495 (2015).","journal-title":"Int. J. Cancer"},{"key":"48074_CR27","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3390\/md21050303","volume":"21","author":"M D\u2019Ambrosio","year":"2023","unstructured":"D\u2019Ambrosio, M. et al. Tisochrysis lutea F&M-M36 mitigates risk factors of metabolic syndrome and promotes visceral fat browning through \u03b23-adrenergic receptor\/UCP1 signaling. Mar. Drugs. 21, 5 (2023).","journal-title":"Mar. Drugs."},{"key":"48074_CR28","doi-asserted-by":"publisher","first-page":"10","DOI":"10.14806\/ej.17.1.200","volume":"17","author":"M Martin","year":"2011","unstructured":"Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet. J. 17, 10\u201312 (2011).","journal-title":"EMBnet. J."},{"key":"48074_CR29","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","volume":"13","author":"BJ Callahan","year":"2016","unstructured":"Callahan, B. J. et al. DADA2: High-resolution sample inference from Illumina amplicon data. Nat. Methods. 13, 581\u2013583 (2016).","journal-title":"Nat. Methods."},{"key":"48074_CR30","doi-asserted-by":"publisher","first-page":"352","DOI":"10.32614\/RJ-2016-025","volume":"8","author":"ES Wright","year":"2016","unstructured":"Wright, E. S. Using DECIPHER v2.0 to analyze big biological sequence data in R. R J. 8, 352\u2013359 (2016).","journal-title":"R J."},{"key":"48074_CR31","unstructured":"R Core Team. R: A language and environment for statistical computing. Version 4.3.1 R Foundation for Statistical Computing, Vienna, Austria. https:\/\/www.R-project.org\/ (2023)."},{"key":"48074_CR32","unstructured":"Signorell, A. DescTools: Tools for descriptive statistics. R package version 0.99.58."},{"key":"48074_CR33","unstructured":"https:\/\/CRAN.R-project.org\/package=DescTools (2024)."},{"key":"48074_CR34","unstructured":"Kassambara, A. rstatix: Pipe-Friendly Framework for Basic Statistical Tests. R package version 0.7.2, https:\/\/CRAN.R-project.org\/package=rstatix (2023)."},{"key":"48074_CR35","unstructured":"Oksanen, J. et al. vegan:Community Ecology Package. R package version 2.6\u20134. Comprehensive R archive network (CRAN). https:\/\/github.com\/vegandevs\/vegan (2022)."},{"key":"48074_CR36","doi-asserted-by":"publisher","first-page":"21033","DOI":"10.1038\/s41598-023-48308-w","volume":"13","author":"G Bacci","year":"2023","unstructured":"Bacci, G. et al. Species-specific gill\u2019s microbiome of eight crab species with different breathing adaptations. Sci. Rep. 13, 21033 (2023).","journal-title":"Sci. Rep."},{"key":"48074_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 1\u201321 (2014).","journal-title":"Genome Biol."},{"key":"48074_CR38","doi-asserted-by":"crossref","unstructured":"Wickham, H., Chang, W., & Wickham, M. H. \u2018ggplot2\u2019. Create elegant data visualisations using the grammar of graphics. Version 2, 1\u2013189 (2016).","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"48074_CR39","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1002\/cam4.46","volume":"2","author":"H Ishikawa","year":"2013","unstructured":"Ishikawa, H. et al. Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: Double-blind, randomized clinical trial. Cancer Med. 2, 50\u201356 (2013).","journal-title":"Cancer Med."},{"key":"48074_CR40","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1158\/1940-6207.CAPR-19-0312","volume":"12","author":"A Mohammed","year":"2019","unstructured":"Mohammed, A. et al. Intermittent dosing regimens of aspirin and naproxen inhibit azoxymethane-induced colon adenoma progression to adenocarcinoma and invasive carcinoma. Cancer Prev. Res. (Phila). 12, 751\u2013762 (2019).","journal-title":"Cancer Prev. Res. (Phila)."},{"key":"48074_CR41","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/S0016-5085(99)70342-2","volume":"117","author":"B Agarwal","year":"1999","unstructured":"Agarwal, B. et al. Lovastatin augments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulindac. Gastroenterology 117, 838\u2013847 (1999).","journal-title":"Gastroenterology"},{"key":"48074_CR42","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.3390\/nu12082251","volume":"12","author":"N Mohebali","year":"2020","unstructured":"Mohebali, N., Ekat, K., Kreikemeyer, B. & Breitr\u00fcck, A. Barrier protection and recovery effects of gut commensal bacteria on differentiated intestinal epithelial cells in vitro. Nutrients 12, 2251 (2020).","journal-title":"Nutrients"},{"key":"48074_CR43","doi-asserted-by":"publisher","first-page":"757718","DOI":"10.3389\/fcimb.2021.757718","volume":"11","author":"K Nie","year":"2021","unstructured":"Nie, K. et al. Roseburia intestinalis: A beneficial gut organism from the discoveries in genus and species. Front. Cell Infect. Microbiol. 11, 757718 (2021).","journal-title":"Front. Cell Infect. Microbiol."},{"key":"48074_CR44","doi-asserted-by":"publisher","first-page":"3502","DOI":"10.1038\/s41467-024-47594-w","volume":"15","author":"SM Holmberg","year":"2024","unstructured":"Holmberg, S. M. et al. The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids. Nat. Commun. 15, 3502 (2024).","journal-title":"Nat. Commun."},{"key":"48074_CR45","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.1136\/gutjnl-2023-330291","volume":"72","author":"X Kang","year":"2023","unstructured":"Kang, X. et al. Roseburia intestinalis-generated butyrate boosts anti-PD-1 efficacy in colorectal cancer by activating cytotoxic CD8\u207a T cells. Gut 72, 2112\u20132122 (2023).","journal-title":"Gut"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48074-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48074-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48074-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:10:50Z","timestamp":1780877450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-48074-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["48074"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-48074-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7216019\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"assertion":[{"value":"25 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The experimental protocols were approved by the Italian Guidelines for Animal Care, DL 26\/2014 under the authorization 496\/2021-PR.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"17654"}}